PROJECT 4 Autonomic Disorders in Parkinson Disease Idiopathic Parkinson disease (PD) is a heterogeneous disorder containing subgroups that have been differentiated by age of onset; occurrence of cognitive impairment; predominance of tremor or of rigidity and hypokinesia; and genetic factors. Identifying patients by subgroup has proved helpful in predicting the rate of disease progression. Multiple autonomic disorders occur in PD, including constipation, sweating dysfunction, urinary difficulty, and orthpstatic hypotension. Cardiac postganglionic sympathetic fibers become degenerated in the early to middle stages of PD, and the stage at which this occurs varies widely. Other nonmotor disorders in PD include difficulties with color discrimination, contrast sensitivity, and olfaction. This project will evaluate the relationship of cardiac denervation to the severity of other autonomic disorders, motor, visual and olfactory functioning in the disease and the rate of progression of these components of the disorder. The overarching hypothesis is that a greater degree of cardiac denervation is associated with greater baseline impairment of autonomic, visual and olfactory functions, and predicts a more rapid decline of these functions as well as motor performance and a more rapid loss of nigrostriatal projections. This hypothesis will be tested by evaluating PD patients at modified Hoehn and Yahr stages 1.0 through 2.0 utilizing positron emission tomography (PET) with [11C]hydroxyephedrine ([11C]HED) to examine cardiac innervation and [11C]dihydrptetrabenazine ([11C]DTBZ) to measure monoaminergic presynaptic nigrostriatal projections, along with specific tests of autonomic function, color discrimination, contrast sensitivity, olfaction, and motor performance. A total of 60 patients will be evaluated at baseline with PET studies of [11C]HED and [11C]DTBZ, along with motor, autonomic, visual, and olfactory performance. The PET studies will be repeated after two years and the results analyzed together with evaluations of motor, autonomic, visual and olfactory functioning. It is predicted that at baseline, early PD patients with cardiac denervation will have greater impairment of other elements of the autonomic nervous system, vision, and olfaction than patients with preserved cardiac innervation, and that these impairments will worsen more rapidly. It is also predicted that in PD patients with cardiac denervation at baseline, decline in motor function and loss of nigrostriatal innervation will occur more rapidly than in patients with preserved cardiac innervation at baseline. The results of this investigation will provide a novel means of characterizing subgroups of patients with PD and of predicting the rate of progression.